The HPV self-collection paradox: boosting cervical cancer screening, struggling with follow-up care
Authors: Runzhi Wang, Jenell S Coleman
Journal: The Lancet Public Health (2023)

Primary high-risk human papillomavirus (HPV) testing is one of the first-line cervical cancer screening strategies in the USA.1Curry SJ Krist AH Owens DK et al.Screening for cervical cancer: US Preventive Services Task Force recommendation statement.JAMA. 2018; 320: 674-686Crossref PubMed Scopus (513) Google Scholar High-risk HPV testing has higher sensitivity for detecting cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) and is less subjective than the Papanicolaou test.2Ronco G Dillner J Elfström KM et al.Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials.Lancet. 2014; 383: 524-532Summary Full Text Full Text PDF PubMed Scopus (1140) Google Scholar Moreover, PCR-based high-risk HPV testing offers the option of unsupervised self-collection of samples, with similar clinical accuracy to clinician-collected samples.3Daponte N Valasoulis G Michail G et al.HPV-based self-sampling in cervical cancer screening: an updated review of the current evidence in the literature.Cancers (Basel). 2023; 151669Crossref Scopus (0) Google Scholar International studies show the efficacy of high-risk HPV self-collection in increasing cervical cancer screening;4Di Gennaro G Licata F Trovato A Bianco A Does self-sampling for human papilloma virus testing have the potential to increase cervical cancer screening? An updated meta-analysis of observational studies and randomized clinical trials.Front Public Health. 2022; 101003461Crossref Scopus (2) Google Scholar however, data are scarce among under-screened US populations. Peyton K Pretsch and colleagues5Pretsch PK Spees LP Brewer NT et al.Effect of HPV self-collection kits on cervical cancer screening uptake among under-screened women from low-income US backgrounds (MBMT-3): a phase 3, open-label, randomised controlled trial.Lancet Public Health. 2023; (published online May 11.)https://doi.org/10.1016/S2468-2667(23)00076-2Summary Full Text Full Text PDF PubMed Google Scholar conducted a phase 3, open-label, randomised controlled trial, among 665 individuals from low-income households in NC, USA, who were under-screened, published in this issue of The Lancet Public Health. Participants were randomly assigned to receive mailed high-risk HPV self-collection kits with appointment scheduling assistance or appointment scheduling assistance alone. The primary outcome was screening uptake, defined as testing negative for high-risk HPV on self-collected samples or attending a clinic appointment. Screening uptake for participants who received mailed high-risk HPV self-collection kits with appointment scheduling assistance was higher than that of participants who received scheduling assistance alone (risk ratio 1·93, 95% CI 1·62–2·31). There were no significant differences in screening uptake based on age, race or ethnicity, insurance, or education. This study is remarkable for several reasons. First, the investigators used an opt-in strategy for distribution of high-risk HPV kits. A meta-analysis reported that opt-in strategies (ie, inviting individuals to order or pick up a kit at a designated site) are less efficacious than opt-out strategies (ie, mailing kits directly to homes without an invitation).4Di Gennaro G Licata F Trovato A Bianco A Does self-sampling for human papilloma virus testing have the potential to increase cervical cancer screening? An updated meta-analysis of observational studies and randomized clinical trials.Front Public Health. 2022; 101003461Crossref Scopus (2) Google Scholar Another randomised controlled trial of high-risk HPV testing on self-collected samples in under-screened US individuals used an opt-out strategy, which also improved screening uptake compared with usual care (RR 1·51, 95% CI 1·43–1·60).6Winer RL Lin J Tiro JA et al.Effect of mailed human papillomavirus test kits vs usual care reminders on cervical cancer screening uptake, precancer detection, and treatment: a randomized clinical trial.JAMA Netw Open. 2019; 2e1914729Crossref PubMed Scopus (27) Google Scholar Since both strategies improved uptake, either could be considered in US populations, although financial costs and limitations of each strategy should be considered. Second, the kit return rate of 78% was impressive, especially since other studies report only 8–20% return rate.6Winer RL Lin J Tiro JA et al.Effect of mailed human papillomavirus test kits vs usual care reminders on cervical cancer screening uptake, precancer detection, and treatment: a randomized clinical trial.JAMA Netw Open. 2019; 2e1914729Crossref PubMed Scopus (27) Google Scholar, 7Sancho-Garnier H Tamalet C Halfon P et al.HPV self-sampling or the Pap-smear: a randomized study among cervical screening nonattenders from lower socioeconomic groups in France.Int J Cancer. 2013; 133: 2681-2687PubMed Google Scholar, 8Cadman L Wilkes S Mansour D et al.A randomized controlled trial in non-responders from Newcastle upon Tyne invited to return a self-sample for human papillomavirus testing versus repeat invitation for cervical screening.J Med Screen. 2015; 22: 28-37Crossref PubMed Scopus (38) Google Scholar One explanation for the differences could be the study design. Pretsch and colleagues5Pretsch PK Spees LP Brewer NT et al.Effect of HPV self-collection kits on cervical cancer screening uptake among under-screened women from low-income US backgrounds (MBMT-3): a phase 3, open-label, randomised controlled trial.Lancet Public Health. 2023; (published online May 11.)https://doi.org/10.1016/S2468-2667(23)00076-2Summary Full Text Full Text PDF PubMed Google Scholar used intensive community outreach methods to recruit participants and randomly assigned them to a trial group after obtaining informed consent; therefore, participants might have been highly motivated to return the kits. Other opt-out studies either enrolled participants under a waiver of informed consent or mailed a study introductory letter with the consent form and test kit. The importance of collaborating with local agencies and community organisations to reach and retain participants cannot be understated. Third, the authors should be commended for recruiting a diverse participant population, with more than half of participants self-reporting as Black, Latina, or Hispanic; uninsured; or unemployed. Although another large US randomised controlled trial enrolled under-screened participants, those participants had health insurance, health-care access, and higher median incomes; were predominately White; and all spoke English.6Winer RL Lin J Tiro JA et al.Effect of mailed human papillomavirus test kits vs usual care reminders on cervical cancer screening uptake, precancer detection, and treatment: a randomized clinical trial.JAMA Netw Open. 2019; 2e1914729Crossref PubMed Scopus (27) Google Scholar This study provides the required evidence that high-risk HPV testing on self-collected samples can be an effective strategy for hard-to-reach populations. Despite the successes of the study, some concerns exist. The primary outcome of screening uptake defined by testing negative for high-risk HPV on self-collected samples, albeit provocative, might be overestimated due to the limitations of the high-risk HPV mRNA assay. The Aptima HPV assay does not have specimen adequacy controls, and if samples are self-collected, the assay has lower sensitivity to detect CIN2+ than if samples are collected by a clinician.9Arbyn M Simon M de Sanjosé S et al.Accuracy and effectiveness of HPV mRNA testing in cervical cancer screening: a systematic review and meta-analysis.Lancet Oncol. 2022; 23: 950-960Summary Full Text Full Text PDF PubMed Scopus (8) Google Scholar Therefore, false-negative results might be recorded from participants who did not collect an adequate sample, alongside true false negatives due to test characteristics. Additionally, there were challenges in follow-up care for diagnosis and CIN2+ treatment. More than 14 000 cervical cancer cases still occur in the USA each year,10National Cancer Institute Surveillance, Epidemiology, and End Results ProgramCancer stat facts: cervical cancer.https://seer.cancer.gov/statfacts/html/cervix.htmlDate accessed: April 11, 2023Google Scholar with Black and Hispanic individuals having the highest incidence. This inequity persists despite similar screening rates between Black individuals and White individuals.11McDaniel CC Hallam HH Cadwallader T Lee HY Chou C Persistent racial disparities in cervical cancer screening with Pap test.Prev Med Rep. 2021; 24101652PubMed Google Scholar Moreover, individuals who are Black, have low socioeconomic status, or do not have insurance are less likely to complete follow-up for atypical screening results.12Benard VB Lawson HW Eheman CR Anderson C Helsel W Adherence to guidelines for follow-up of low-grade cytologic abnormalities among medically underserved women.Obstet Gynecol. 2005; 105: 1323-1328Crossref PubMed Scopus (81) Google Scholar Similarly, in this trial, more than half of participants who tested positive for high-risk HPV, had an invalid result, or were assigned to the control group did not complete follow-up. Thus, it is possible that any gains achieved by increasing screening might not be reflected in decreased cancer incidence. Furthermore, rates of follow-up and treatment are probably even lower in real-world clinical settings, which raises the concern for further exacerbating existing health inequities. In summary, the study by Pretsch and colleagues5Pretsch PK Spees LP Brewer NT et al.Effect of HPV self-collection kits on cervical cancer screening uptake among under-screened women from low-income US backgrounds (MBMT-3): a phase 3, open-label, randomised controlled trial.Lancet Public Health. 2023; (published online May 11.)https://doi.org/10.1016/S2468-2667(23)00076-2Summary Full Text Full Text PDF PubMed Google Scholar adds valuable insights into the potential benefits of self-collected samples for high-risk HPV testing to increase cervical cancer screening among under-screened individuals in the USA. But to ensure that increased screening uptake translates to decreased cancer incidence rates, the entire cervical cancer prevention process, from screening to treating precancers, requires optimisation. Optimisation includes policy reforms to remove financial barriers to diagnostic tests and treatment; community outreach and education campaigns; and improved access to quality care through transportation services, expanded Medicaid eligibility, and skilled clinicians. Additionally, future research should include pragmatic studies to assess real-world scenarios and investigate barriers to follow-up care and treatment. We declare no competing interests. Effect of HPV self-collection kits on cervical cancer screening uptake among under-screened women from low-income US backgrounds (MBMT-3): a phase 3, open-label, randomised controlled trialAmong under-screened women from low-income backgrounds, mailed HPV self-collection kits with scheduling assistance led to greater uptake of cervical cancer screening than scheduling assistance alone. At-home HPV self-collection testing has the potential to increase screening uptake among under-screened women. Full-Text PDF Open Access